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Stimulation of Phagocytic Release of Neutral Protease from Human Neutrophils by Cholinergic Amines and Cyclic 3',5'-Guanosine Monophosphate¹

From the Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112

Abstract

The purpose of this study was to elucidate the actions of cholinergic agents and cyclic 3',5'-guanosine monophosphate (cyclic GMP) on phagocytic release of a lysosomal neutral protease from human neutrophils in the presence of aggregated IgG-rheumatoid factor complex. Neutrophils (5 x 10⁶) and complex were incubated in a balanced salt solution, pH 7.4, at 37°C for 15 min in the absence and presence of various cholinergic agents and cyclic GMP analogs. Acetylcholine, acetyl -methylcholine, carbamylcholine, and pilocarpine, but not choline, provoked a 74% to 94% increase in enzyme release at 10^-7 M. Atropine, but not hexamethonium, blocked the accelerating action of acetylcholine on enzyme release. Cyclic GMP as well as three of its analogs also enhanced release of neutral protease from phagocytosing human neutrophils (71% to 136% increase at 10^-7 M). Guanosine 5'-monophosphate or triphosphate did not provoke enzyme release and atropine did not block the effect of cyclic GMP. Neither the cholinergic agents nor cyclic GMP affected release of cytoplasmic lactate dehydrogenase, thus indicating maintenance of cell viability during lysosomal enzyme release. The data suggest that human neutrophils have muscarinic receptors that respond to cholinergic agents by acceleration of lysosomal enzyme release, perhaps via a mechanism involving intracellular cyclic GMP.

Footnotes

¹ This research was supported by grants from the Pharmaceutical Manufacturers Association Foundation and Merck & Co., Inc.

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